"The serum amplifies everything that is inside, so good becomes great; bad becomes worse. This is why you were chosen. Because the strong man who has known power all his life, may lose respect for that power, but a weak man knows the value of strength, and knows... compassion."

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"You picked a most inopportune time to become a faliure, Herr Erskine. But I knew you would fail. All I would have to do is bide my time. And an opportunity for me to provide a technological solution to the übermensch soldier program would present itself.""My serum did not fail. It did...exactly what I designed it to do. It enhances...what is already within. It is Herr Schmidt...who has failed...at being human."

Erskine began developing his serum in 1930 while still in Germany. In 1940, the formula was tested on the SS general Johann Schmidt, turning him into Red Skull in the process.[1] Erskine would later describe to Steve Rogers how the formula wasn't ready for use, and how the serum's personality amplifying effects made Schmidt into the evil man he became.[2]

After Erskine escaped to America, he joined the Strategic Scientific Reserve (predecessor to the modern organization: S.H.I.E.L.D.). There he took part in Project Rebirth, a project to create a Super Soldier for the Allied forces. Using Vita Radiation to unlock the serum's potential, Erskine successfully used the serum on Steve Rogers, who became the hero Captain America. Unfortunately, the scientist was killed and the last vial of the original serum was destroyed by HYDRA spy Heinz Kruger, with the last remnants of the serum remaining in Rogers' DNA.[2]

In October 1943, Sergeant James Buchanan Barnes of the U.S. Army was captured by HYDRA and sent to work at the top secret weapons facility in the Austrian Alps. When he was too weak to work, Dr. Zola used him as a subject for his experiments with his own version of the Super Soldier Serum. Barnes was injected with the serum shortly before the prisoners were liberated by Captain America a month later.[2][3]

During the first icy months of 1945, Captain America and Sergeant Barnes led an attack on the HYDRA train that was transporting Dr. Zola to another base. During the fight, Bucky fell from the train, falling into an icy river below, whose cold waters no ordinary man could survive. However, thanks to the serum's effect on his body, Barnes was able to survive, though at the cost of his left arm.[3]

"You must realize that what I'm about to tell you is very sensitive, both to me and to the Army. You know that we have a Bio-Force Department, and that we had a bio-force enhancement research project developed during World War II...""A Super-Soldier."

In 2001, General Ross of the US Army revived the Bio-Tech Force Enhancement Project, a secret project set-up after the relative failure of Project Rebirth. A failed attempt to reproduce the serum with added bouts of Gamma Radiation led to the accident that turned Bruce Banner into the Hulk. Banner was later forced to flee from Ross, who employed the British soldier Emil Blonsky to track him down. General Ross, eager to sustain Blonsky's will to fight, gave him an injection of a similar serum, which gave him abilities similar to those of Captain America. Later combination with the altered serum in Banner's blood turned Blonsky into the Abomination.[4]

As of 2013, scientists recreated a very similar version of the serum as one of the components of the Centipede Serum, designed to give a person superhuman abilities. This serum was mixed with the Extremis virus, Gamma Radiation and technology from the Chitauri for injection.[5]

The raw serum's general properties seemed to be enhanced strength and senses, as well as emphasizing the user's key personality traits. Johann Schmidt's evil meant that the serum ripped the flesh from his skull, while Steve Rogers' bravery enhanced his body to the peak of human ability. Emil Blonsky's strength and fast regenerative abilities were part of his love of fighting.

When saturated with Vita Radiation, the serum worked more successfully. Gamma rays were believed by Bruce Banner to work similarly, but instead corrupted the serum's effects and turned him into the raging monster known as the Hulk.

The serum's effect on the body is to increase the molecular density of cellular fibers (skin and muscle) through synthetic proteins. However, the serum not only enhances the body and mind but also brings out and enhances what the person truly is.

These personality traits are brought to the surface and manifest physically on the subjects:

Johann Schmidt/Red Skull took the prototype serum. Schmidt's external transformation is that of a living Red Skull. Schmidt has always wanted to be seen as removed from mere ordinary men around him, and as such his appearance is a reflection of that.

Steve Rogers/Captain America was the only successful attempt. Erskine's insistence to find a "good man" is an understatement. In Steve Rogers he found someone with unquestionable moral value who only wanted to be the best he could be and his physical transformation is a reflection of that.

Bruce Banner/Hulk was given a very similar serum and a deadly amount of Gamma Radiation. The combination turned him into an aggressive, giant, green, muscular beast. Banner reverted to his original state, but would transform again in the future whenever his heart rate became too high or he became extremely angry.

Emil Blonsky/Abomination had the serum injected into his spine. Blonsky's extra physical manifestations, protruding skeletal structure, takes a while to materialize. Due to the replacement of the Vita Radiation with the Gamma Radiation in Banner's blood, the serum kicked into overdrive, transforming Blonsky into a Hulk-sized version of himself with a green tinge, with the external bone structure being a reflection of the tough monstrous fighter that he shows himself to be.

Chan Ho Yin/Scorch was also injected with the Centipede Serum. This serum increased his previous pyrokinetic powers. Before this, Chan was ordered by S.H.I.E.L.D. to keep his powers secret, but he had always wanted to be remembered by his gift. After being administered with the serum and betrayed by draining his fire-resistant blood platelets, Chan become mentally unstable and killed at least two people before being neutralized himself.

The version of the formula given to Blonsky is labelled as having been created by a "Dr Reinstein". In the comics, "Reinstein" was an alias used by two doctors: Erskine and his successor who attempted to recreate the formula after Erskine's assassination. The latter's efforts used African-American soldiers as expendable guinea pigs and none survived, except Isaiah Bradley in the main 616 comics[7] and Nick Fury in the Ultimate comics.[8]